DESCRIPTION (Applicant's abstract reproduced verbatim): The aim of this research application is to study functional consequences of a decreased PKA activity in early mouse development. It involves analyzing a PKA-deficient mouse generated with only one functional catalytic allele left in the PKA system. This PKA-deficient mouse develops severe neural tube defects leading to spina bifida and this suggests a specific requirement for PKA in neural tube formation. The proposed project includes examination of gene expression, cell proliferation and cell death in the defective neural tube. Rescue experiments will be performed to further determine the molecular basis for the neural tube defects in the PKA-deficient mice. This research will increase our understanding of the function of PKA in embryonic development, and the molecular and cellular basis of neurulation, which may lead to improved treatment for human neural tube defects.